Szenohradszky J, Lau M, Brown R, Sharma M L, Fisher D M
Department of Anesthesia, University of California, San Francisco 94143-0648, USA.
Anesthesiology. 1995 Jul;83(1):83-7. doi: 10.1097/00000542-199507000-00010.
An investigation suggested that neostigmine may not effectively antagonize mivacurium, presumably because neostigmine impairs mivacurium's metabolism. However, the effect of neostigmine on mivacurium's metabolism in vivo has not been reported. Therefore, the effect of neostigmine on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion was determined.
Mivacurium was infused in five patients to maintain 90% depression of adductor pollicis twitch tension, then 50 micrograms/kg intravenous neostigmine was administered without altering the mivacurium infusion. Peak twitch tension after neostigmine, plasma cholinesterase activity, and mivacurium concentrations before and after neostigmine were measured. Five additional patients were given 50 micrograms/kg neostigmine to antagonize block due to continuous infusions of vecuronium.
Neostigmine produced less antagonism of mivacurium (39 +/- 11%) than of vecuronium (54 +/- 9%, P < 0.05). Neostigmine decreased plasma cholinesterase activity and increased plasma concentrations of the trans-trans and cis-trans stereoisomers of mivacurium (P < 0.05).
Neostigmine is less effective at antagonizing the neuromuscular effect of mivacurium than that of vecuronium during constant infusion. Neostigmine increases plasma mivacurium concentrations, likely explaining its limited efficacy. Our results confirm that neostigmine impairs the metabolism of mivacurium in vivo and may explain the observation that neostigmine may not effectively antagonize mivacurium-induced block.
一项调查表明,新斯的明可能无法有效拮抗米库氯铵,推测原因是新斯的明会损害米库氯铵的代谢。然而,新斯的明对米库氯铵体内代谢的影响尚未见报道。因此,本研究测定了持续输注米库氯铵期间新斯的明对神经肌肉功能和血浆米库氯铵浓度的影响。
对5例患者输注米库氯铵以维持拇收肌抽搐张力抑制90%,然后静脉注射50微克/千克新斯的明,同时不改变米库氯铵的输注速率。测定新斯的明给药后的抽搐张力峰值、血浆胆碱酯酶活性以及新斯的明给药前后的米库氯铵浓度。另外5例患者给予50微克/千克新斯的明以拮抗维库溴铵持续输注所致的阻滞。
新斯的明对米库氯铵的拮抗作用(39±11%)小于对维库溴铵的拮抗作用(54±9%,P<0.05)。新斯的明降低了血浆胆碱酯酶活性,并增加了米库氯铵反式-反式和顺式-反式立体异构体的血浆浓度(P<0.05)。
在持续输注期间,新斯的明拮抗米库氯铵神经肌肉效应的效果不如维库溴铵。新斯的明增加了血浆米库氯铵浓度,这可能解释了其疗效有限的原因。我们的结果证实新斯的明在体内损害米库氯铵的代谢,这可能解释了新斯的明可能无法有效拮抗米库氯铵诱导的阻滞这一现象。